The purpose of the proposed research is to investigate the role of the cytoskeleton (CS) in human prostatic epithelium. The CS has recently been implicated in a variety of cell functions, but presently very little is known about this important system in human prostate. Functions of the CS relate to cell shape, cell division, cell migration, ion regulation and cell secretion. Important cause-effect relationships may exist between cell shape and cell division. Clearly, the characterization of the CS (microtubules, microfilaments and intermediate filaments) as well as important regulatory proteins, e.g., calmodulin, stands as a significant challenge in the field of prostate cell biology. After initial characterization of the CS of normal, hyperplastic and neoplastic prostatic epithelium, we propose to undertake experiments designed to modulate cytoskeletal structure and function and determine the effect on cell proliferation in vitro. This will involve agents or conditions known ot modify specific elements of the cytoskeleton. In each case the results will be compared with non-treated cells. This phase is expected to reveal new concepts concerning the role of the CS in phenotypic alterations that characterize normal, hyperplastic and neoplastic prostatic epithelium. The results have implications for the biology of prostatic epithelium as well as for the future therapeutic interventions. The specific aims are summarized as follows: 1. to identify and characterize CS components (tubulin, actin, keratin, calmodulin) of epithelial cells of normal, hyperplastic and neoplastic human prostate in vivo utilizing immunocytochemical methods. 2. To compare normal, hyperplastic and neoplastic human prostate prior to culture, with those of explant and cell outgrowths of the same tissues in vitro and with monolayer cultures of neoplastic cell lines, and 3.to manipulate individual components of the cytoskeleton in a systematic fashion with modifiers, such as colcemid, Taxol, A23187, etc., and determine the effects of these modifiers on cell shape and replication using combined immunocytochemistry and autoradiography.